Genotoxicity of 1-nitropyrene and 2,4,7-trinitro-9-fluorenone to mammalian cells.
Nitroarenes are ubiquitous environmental pollutants displaying potent genotoxicity in bacterial and mammalian cells. In this study, 2,4,7-trinitro-9-fluorenone (TNF) was more potent than 1-nitropyrene (1-NP) in eliciting genotoxic responses in 4 mammalian cell lines. All 4 cell types were capable of activating the nitroarenes, since no special incubation conditions were required. Inhibition of normal DNA synthesis and cytotoxicity were significantly increased with TNF in a dose range of 0.2-5 micrograms/ml for human teratocarcinoma (PA1) cells, mouse Sertoli (TM4) cells, rat hepatoma (RL12) cells, and human-Chinese hamster ovary (CHO-K1) cells. For 1-NP, a dose range of 10-20 micrograms/ml was required to achieve comparable results for the respective cell lines. Only the RL12 and CHO-K1 cells showed recovery of normal DNA synthesis when TNF or 1-NP was removed from the medium. The other cell types showed little or no recovery up to 42 h after removal of the nitroarene. In exclusively studying TNF, the induction of sister-chromatid exchanges (SCEs) and a delay in cell cycle as monitored by harlequin chromosomes, were observed at a concentration range of 0.003-0.2 microgram/ml in PA1, TM4, and RL12 cells. In CHO-K1 cells, TNF at 0.001-1 microgram/ml was clearly mutagenic at the hprt locus.
Rodriguez
H
H
Biology Department, Boston University, MA 02215.
Murison
G L
GL
D000818:Animals; D002875:Chromosomes / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005449:Fluorenes / Q000633:toxicity*; D006801:Humans; D006822:Hybrid Cells; D008322:Mammals; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D011721:Pyrenes / Q000633:toxicity*; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D005449:Fluorenes; D009153:Mutagens; D011721:Pyrenes; D004247:DNA; C005644:2,4,7-trinitrofluorenone; C032668:1-nitropyrene